Gurgel, Clarissa Araújo. Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento.Conselho Nacional de Desenvolvimento Científico e Tecnológico” (CNPq); Coordenação de Aperfeiçoamento de Ensino Superior (CAPES).This study investigated components of the Hedgehog (HH) signaling pathway (SHH, GLI1), cyclin D1, and smooth muscle actin (SMA) in central giant cell granulomas (CGCG). The relationship between these proteins and myofibroblasts was also studied. Material and methods: Twelve cases of non‐aggressive CGCG and 11 cases of aggressive CGCG were studied using immunohistochemistry for SHH, GLI1, Cyclin D1, and SMA. Results: Associations between all proteins in non‐aggressive and aggressive CGCG were not significant (P > .05). All cases of CGCG showed significantly higher expression of SMA compared with the other proteins (P < .01). A positive correlation (P = .04) was only observed between SHH and GLI1 for all cases of CGCG. Furthermore, a positive correlation between SHH and GLI1 in non‐aggressive CGCG (P = .04) and between GLI1 and cyclin D1 in aggressive CGCG (P = .03) were observed. There was also a negative correlation between the expression of SHH and SMA in non‐aggressive CGCG (P = .031). Conclusions: This study provided insights into the activation of the HH signaling pathway in CGCG. In addition, the activation of this pathway (SHH and GLI1) might play some role in the differentiation of stromal myofibroblasts, although these markers including Cyclin D1 and SMA do not indicate aggressiveness of the CGCG. Furthermore, this myofibroblastic differentiation process would occur at the expense of maturation of these lesions.2020-01-06